A tumor suppressor protein inhibits the transformation of a normal cell to a cancer cell and, therefore, loss of its activity, e.g., mutation, may contribute to the malignant transformation of a normal cell (Weinberg R A, Science, 254, 1138-1146 (1991); and Klein G., FASEB J, 7,821-825 (1993)).
Over twenty tumor suppressor genes and cancer-predisposition syndromes caused by mutation thereof have been reported (Haber D A et al., Lancet, 351, 1-8 (1998)). Among these, alterations of the coding sequences of the p53 tumor suppressor gene have been found to be responsible for most of the human cancers of genetical origin (Weinberg R A, vide supra; Klein G., vide supra; and Bishop J M, Cell, 64, 235-248 (1991)). However, only a small portion, i.e., 2 to 11%, of cervical cancer tissues exhibit p53 mutation (Crook T et al., Lancet, 339, 1070-1073 (1992); and Busby-Earle RMC et al. (Br. J. Cancer, 69, 732-737 (1994)) have suggested the existence of other tumor suppressor genes in case of cervical cancer. Therefore, there has existed a need to identify a gene which suppresses cervical cancer.